Sodium nitrite negatively affects reproductive ability and offspring survival in female mice

Sodium nitrite (NaNO₂) is an industrial chemical that is frequently used as a food additive to prevent botulism and enhance glossiness, such as curing meat. In addition, in some regions, water source NaNO₂ concentrations exceed standard regulatory levels. Whether the excessive intake of NaNO₂ has toxic effects on female fertility and fetal development remain unknown. In this study, we administered ICR mice control saline, low-dose NaNO₂ (60 mg/kg/day), or high-dose NaNO₂ (120 mg/kg/day) by intragastric gavage for 21 days. We then assessed oocyte morphology, spindle-chromosome dynamics, mitochondrial distribution, ATP content, apoptotic cell numbers, DNA damage levels, histone modifications, reactive oxygen species (ROS) levels, and offspring survival. Results showed that NaNO₂ treatment decreased oocyte number, impaired polar body extrusion, and increased zona pellucida thickness in oocytes. Furthermore, NaNO₂ disrupted MII spindle integrity, caused abnormal mitochondrial distribution, decreased ATP content, and increased levels of ROS and H3K4me2. Moreover, the number of oocytes in early stages of apoptosis and with levels of DNA damage increased in NaNO₂-treated mice along with decreased offspring numbers and survival rates. We demonstrated the negative effects of NaNO₂ on female reproductive abilities in mice.